Principal Investigator: Christopher R. Jacobs, PhD Investigators: Henry J. Donahue, PhD and R. Lane Smith, PhD Project Category: Bone & Joint and Osteoporosis - 2005 Objective: Bone cells occupy fluid filled voids (lacunae) in the mineralized matrix and interconnected by small tubes (canaliculi). As the bone matrix is cyclically loaded, fluid flows in the lacunar-canalicular network from regions of high matrix strain to low matrix strain and back in an oscillatory fashion. Although, it has been demonstrated that bone cells respond to steady and pulsatile fluid flow with a transient elevation in intracellular calcium concentration, increased release of paracrine factors, and increased gene transcription, our preliminary data indicate that these responses are fundamentally different from those observed for oscillating flow. The central hypotheses of the most recently awarded five year funding period is that oscillatory fluid flow regulates bone cell metabolism via a molecular mechanism involving forces transmitted by the cytoskeleton to focal adhesion sites and integrins. The result of this project will be specific knowledge of the molecular mechanism responsible for transduction of mechanical loads in bone. Research Plan: This project is divided into four specific aims:
Work Accomplished: Our competing continuation application was successful and we were awarded an additional five years of support. Work the aims involved in this funding period has just begun. Expected Outcome: The long-term goal of these studies is to better understand the how mechanical loading influences the behavior of bone. Increased understanding of this relationship will lead to the identification of novel targets of therapeutic interventions in bone diseases with a mechanical component such as osteoporosis Funding Source: NIH Funding Status: Active
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